Myeloid Derived Suppressor Cells and Their Role in Diseases

Abstract

Abstract:Myeloid derived suppressor cells (MDSCs) are a heterogeneous population of myeloid progenitors that can play a major role in tumour development and chronic inflammation. The importance of the suppressive function of MDSCs was first suggested by studies involving cancer patients and cancer-bearing mice. In addition, recent studies have demonstrated that MDSCs can also be involved in many other pathological conditions. MDSCs have unique ways of abrogating an immune response in addition to those utilised by other immune-suppressive cell types, for example via the induction of arginase-1 and consequent upregulation in reactive oxygen species (ROS) production. Due to their heterogeneity, they further can express a variety of lineage markers, which overlap with other myeloid cell types such as Gr1, CD11b, MHCII lo , Ly6C and Ly6G, making it difficult to identify them by surface phenotype alone. The disparity between mouse and human MDSCs further complicates the identification of these elusive cell populations. In this review, we will summarise the recent updates on the methods for eliciting and studying different MDSC subsets, including newly proposed surface phenotypes, as well as insights into how their function is being characterised in both mice and humans. In addition, exciting new discoveries suggesting their involvement across a number of different pathological settings, such as sepsis, autoimmunity and Leishmaniasis, will be discussed.

MicroRNA 21 (miR-21) and miR-181b Couple with NFI-A To Generate Myeloid-Derived Suppressor Cells and Promote Immunosuppression in Late Sepsis

“…Despite this phenotypic heterogeneity of mouse and human MDSCs, both monocytic and granulocytic subpopulations are immunosuppressive (15), although they may suppress the immune response by different mechanisms (14,16). Upon activation by tumor-or inflammation-driven factors, MDSCs express/produce immunosuppressive mediators, including arginase 1, inducible nitric oxide synthase (iNOS), reactive oxygen species (ROS), transforming growth factor ␤ (TGF-␤), interleukin 10 (IL-10), and cyclo-oxygenase 2 and prostaglandin E2 (12,14,16). These mediators then inhibit T cell proliferation and activation, induce T regulatory cells, and inhibit innate immune cell functions, thus suppressing both innate and adaptive immunity (12)(13)(14).…”

“…Upon activation by tumor-or inflammation-driven factors, MDSCs express/produce immunosuppressive mediators, including arginase 1, inducible nitric oxide synthase (iNOS), reactive oxygen species (ROS), transforming growth factor ␤ (TGF-␤), interleukin 10 (IL-10), and cyclo-oxygenase 2 and prostaglandin E2 (12,14,16). These mediators then inhibit T cell proliferation and activation, induce T regulatory cells, and inhibit innate immune cell functions, thus suppressing both innate and adaptive immunity (12)(13)(14). Interestingly, recent studies reported that factors that eliminate MDSCs can overcome immune suppression and improve the immune response.…”

“…In addition, we have shown that MDSCs from late sepsis are immunosuppressive, as they produced immunosuppressive cytokines and attenuated early sepsis hyperinflammation when transferred into mice undergoing sepsis response (8). Although several soluble factors, which can all be produced in the inflammatory microenvironment, such as vascular endothelial growth factor (VEGF), granulocyte colony-stimulating factor and monocyte colony-stimulating factor (M-CSF), and inflammatory cytokines, have been suggested to induce MDSC generation and expansion in the context of cancer (11)(12)(13)(14), the molecular mechanism that generates MDSCs in sepsis remains unknown.…”

“…The immature phenotypes and suppressive activities are the hallmark of these cells, as they potently suppress T cell and innate-immunity cell functions (13)(14)(15). Phenotypically, mouse MDSCs are characterized by the coexpression of the myeloid differentiation markers CD11b and Gr1 (12,16).…”

Interleukin-10 produced by myeloid-derived suppressor cells is critical for the induction of tregs and attenuation of rheumatoid inflammation in mice

“…It is well accepted that MDSCs can suppress T cell function via soluble mediators such as arginase-1 and iNOS 1,3,25 . Therefore, arginase-1 or iNOS could mediate the immunoregulatory and anti-arthritic effects of MDSCs.…”